Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.

MicroRNA-423 (miR-423) is highly expressed in breast cancer (BC). Previously, our group showed that the SNP rs6505162:C>A located in the pre-miR-423 was significantly associated with increased familial BC risk in patients with a strong family history of BC. Therefore, in this study, we evaluated the functional role of rs6505162 in mammary tumorigenesis in vitro to corroborate the association of this SNP with BC risk. We found that rs6505162:C>A upregulated expression of both mature miR-423 sequences (3p and 5p). Moreover, pre-miR-423-A enhanced proliferation, and promoted cisplatin resistance in BC cell lines. We also showed that pre-miR-423-A expression decreased cisplatin-induced apoptosis, and increased BC cell migration and invasion. We propose that the rs6505162-A allele promotes miR-423 overexpression, and that the rs6505162-A allele induces BC cell proliferation, viability, chemoresistance, migration, and invasion, and decreases cell apoptosis as a consequence. We suggest that rs6505162:C>A is a functional SNP site with potential utility as a marker for early diagnosis, prognosis, and treatment efficacy monitoring in BRCA1/2-negative BC patients, as well as a possible therapeutic target.

La enfermedad por coronavirus 2019 (COVID-19), causada por el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2), destaca por su alto nivel de transmisibilidad y morbilidad en la población general, pudiendo generar cuadros letales en individuos con enfermedades de base. Dicha infección se caracteriza principalmente por afectar al sistema respiratorio, produciendo un cuadro de síndrome gripal, asociado con mialgias, cefaleas, anosmia y ageusia, entre otros. Los mecanismos inmunológicos dirigidos contra el SARS-CoV-2 están mediados por células inmunes innatas que expresan receptores capaces de reconocer patrones moleculares asociados a este patógeno, relacionado a un ambiente pro-inflamatorio, necesario para controlar la infección, y que participa en la activación de la respuesta inmune adaptativa. Este proceso está representado por la producción de anticuerpos contra antígenos virales por parte de linfocitos B, y por la activación de linfocitos T CD4+ y CD8+. Sin embargo, en ciertos individuos, la respuesta inmune puede ser excesiva, produciéndose un aumento significativo en los niveles de distintas citoquinas pro-inflamatorias, causando un cuadro denominado “tormenta de citoquinas”. A nivel pulmonar, dicho cuadro causa infiltración leucocitaria y daño en el tejido, lo que afecta severamente la función de este tejido, lo que puede llegar a comprometer la vida del individuo. Una de las principales estrategias para disminuir el número de cuadros severos y graves asociados a COVID-19 ha sido el desarrollo de vacunas contra este virus, lo cual ha sido clave para limitar la propagación de este agente y reducir el riesgo de mortalidad.